Published ahead of print in the Journal of the American College of Cardiology, the TARGET (Targeted left ventricular lead placement to guide cardiac resynchronisation therapy) study shows that using speckle-tracking echocardiography to target left ventricular lead placement for cardiac resynchronisation therapy (CRT) significantly improves the rate of response and clinical status compared with conventional therapy.
The significant number of patients who fail to respond to CRT continues to be a problem in the management of heart failure, and there has been a drive to better identify predictors of response to CRT. As some studies have shown that placing the left ventricular lead at the most delayed region is associated with a better clinical response, the aim of TARGET was to compare prospectively targeting the left ventricular lead at the most delayed viable segment, as defined by speckle-tracking echocardiography, compared with standard therapy (CRT with left ventricular lead placed at a lateral or posterolateral branch of the coronary sinus).
Fakhar Khan, Papworth Hospital, Cambridge, UK, and co-authors randomised patients with advanced heart failure and who were eligible for CRT into two groups: in group one, the left ventricular lead was positioned (or an attempt was made to position) at the most delayed region (as identified by 2D radial strain imaging); in group two, left ventricular lead was placed without echocardiographic guidance. Khan et al reported: “The latest segment of contraction was identified as the most delayed peak from the onset of QRS duration in both the basal and mid short-axis views. When >1 segment was equally delayed, then placement of the left ventricular lead at either site was considered to be concordant.”
The primary endpoint of the study was a comparison of response rate between groups one and two, and second endpoints included clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and the combined endpoint of all-cause mortality and hospitalisation due to heart failure.
Of the 103 patients in the TARGET group, 70% were classified as responders compared with 55% of 104 patients in the control group (p=0.031)-this lead to an absolute difference in primary response rates of 15% between the two groups. Khan et al wrote: “The number needed to treat by using a targeted approach to left ventricular lead placement to gain an additional responder is 6.6”. Compared with patients in the control group, significantly more patients in the TARGET group had a ≥1 improvement in NYHA functional class (83% for the TARGET group vs. 65% for the control group; p=0.003). Also, significantly less patients in the TARGET group met the combined secondary endpoint of all-cause mortality and hospitalisation due to heart failure (p=0.031 for the comparison) and this was driven by the higher rate of hospitalisation due to heart failure in the control group. Khan et al also performed a univariable and multivariable regression analysis to determine which parameters predicted left ventricular reserve remodelling. They wrote: “Multivariate analysis suggests that the greatest benefit is demonstrated in patients with a concordant left ventricular lead at sites free of [myocardial] scar, with significantly lower responses in patients with either a left ventricular lead remote to the latest site of contraction or when pacing scar.”
Khan et al concluded: “An individualised approach to left ventricular lead placement should be considered in all patients undergoing CRT for advanced heart failure to yield a significant improvement over current routine practice.”
Writing in accompanying editorial, Jalal Ghali, DMC Cardiovascular Institute/Wayne State University, Detroit, Michigan, USA, said: “Although the findings of this trial may not mandate the selection of the most delayed viable segment when CRT is being considered, they do call into question the wisdom of not selecting the most likely responders when an invasive and costly procedures such as CRT is initiated.”